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PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

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PURPOSE: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. MATERIAL AND METHODS: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. RESULTS: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. CONCLUSIONS: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

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PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

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PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

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BACKGROUND: There is a lack of knowledge about the career paths and employment situation of young medical oncologists. The aim of our study was to evaluate the current professional standing of these professionals in Spain. METHODS: The Spanish Society of Medical Oncology + MIR section conducted a national online survey in May 2021 of young medical oncology consultants (< 6 years of expertise) and final year medical oncology residents. RESULTS: A total of 162 responses were eligible for analysis and included participants from 16 autonomous communities; 64% were women, 80% were consultants, and 20% were residents. More than half of the participants performed routine healthcare activity and only 7% research activity. Almost three quarters (73%) were subspecialized in a main area of interest and almost half of these chose this area because it was the only option available after residency. Half of the respondents (51%) considered working abroad and 81% believed the professional standing in Spain was worse than in other countries. After finishing their residency, only 22 were offered a job at their training hospital. Just 16% of participants had a permanent employment contract and 87% were concerned (score of ≥ 5 on a scale of 1-10) about their job stability. In addition, one quarter of the participants in our study showed an interest in increasing their research activity. CONCLUSIONS: The choice of subspecialty in medical oncology may depend on job opportunities after residency rather than personal interest. The abundance of temporary contracts may have influenced the job stability concerns observed. Future mentoring strategies should engage in building a long-term career path for young medical oncologists.

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This work is aimed to assess potential risk associated with the presence of metals and metalloids in soil at "Playa Las Petroleras" sector, located in Antofagasta (Chile). The zone under study has been affected by four oil spill events. This sector is located in an urban area by the sea. So, it has a great social and environmental relevance. The concentrations of 15 elements in soil samples were assessed, four of them presenting potential ecological risk: As, Co, Cu, and Pb. Nine pollution indices were applied to data: four single pollution indices and five integrated pollution indices to assess soil pollution. The single pollution indices show that the site bears potential ecological and environmental risk due to the presence of Cu, the site being classified as highly contaminated owing to a severe enrichment of this metal. For Co, all the indices allow classifying the site as little or uncontaminated, while the level of As and Pb pollution could be considered as ranging from uncontaminated to moderately contaminated. The integrated pollution indices show that average concentrations are highly contaminated mainly owing to the presence of Cu.

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PURPOSE: Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. RESULTS: 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84-19.16 vs. 19 months 95% CI 16.11-21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p < 0.05). 291 patients with melanoma were enrolled. There was a 5.8% incidence rate of VTE/AT during follow-up. Median OS was lower in the VTE/AT group (10 months 95% CI 0.0-20.27 vs. 29 months 95% CI 19.58-36.42; p = 0.034). NLR and lactate dehydrogenase (LDH) at the beginning of ICI were predictor variables for VTE/AT (p < 0.05). CONCLUSIONS: ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS.

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BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). METHODS: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. RESULTS: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

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In a previous report we described a multivariate approach to discriminate between the different response mechanisms operating in Escherichia coli when a steady, continuous culture of these bacteria was perturbed by a glycerol pulse (Guebel et al., 2009, Biotechnol Bioeng 102: 910-922). Herein, we present a procedure to extend this analysis when multiple, spaced pulse perturbations (glycerol, fumarate, acetate, crotonobetaine, hypersaline plus high-glycerol basal medium and crotonobetaine plus hypersaline basal medium) are being assessed. The proposed method allows us to identify not only the common responses among different perturbation conditions, but to recognize the specific response for a given stimulus even when the dynamics of the perturbation is unknown. Components common to all conditions are determined first by Generalized Principal Components Analysis (GPCA) upon a set of covariance matrices. A metrics is then built to quantify the similitude distance. This is based on the degree of variance extraction achieved for each variable along the GPCA deflation processes by the common factors. This permits a cluster analysis, which recognizes several compact sub-sets containing only the most closely related responsive groups. The GPCA is then run again but is restricted to the groups in each sub-set. Finally, after the data have been exhaustively deflated by the common sub-set factors, the resulting residual matrices are used to determine the specific response factors by classical principal component analysis (PCA). The proposed method was validated by comparing its predictions with those obtained when the dynamics of the perturbation was determined. In addition, it showed to have a better performance than the obtained with other multivariate alternatives (e.g., orthogonal contrasts based on direct GPCA, Tucker-3 model, PARAFAC, etc.).

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Pulse experiments in continuous-culture are a valuable tool in microbial physiology research. However, inferences become difficult when the cell response is followed by monitoring many biochemical variables or when several types of perturbations are compared. Moreover, there is no objective criterion to delimit the time-window, so that the recorded responses will render valid inferences. Hence, we have investigated the capability of a multivariate approach to deal with complex data from a previously described series of pulse experiments. Data are concerned with 12 biochemical variables that were monitored when an anaerobic, steady-continuous culture of E. coli O74K74 was disturbed by six types of pulses (glycerol, fumarate, acetate, crotonobetaine, hypersaline plus high-glycerol basal medium and crotonobetaine plus hypersaline basal medium). Our analysis determined the instantaneous uptake rate for the pulsed metabolite (Dynamical Chemical-Balances), reduced the multivariate observations to one response curve (Principal Component Analysis) and determined the optimal time-window (Cluster Analysis). Finally, input-output data were filtered (Orthogonal Signal Correction) while both blocks were mathematically connected (Partial Least-squares Regression). This systematic approach allowed us to detect several relevant patterns not previously revealed: (i) Glycerol uptake rate did not follow a Michaelian kinetics but showed a biphasic dependence on glycerol concentration; noticeably, net uptake decreased 136-fold despite the high availability of glycerol in the milieu. (ii) The structure of the bacterial response changed during time the glycerol-disturbance lasted (2 h), hence analyses had to be limited to the early response (time from 0 to 5 min). (iii) By mathematically relating the input (glycerol uptake rate) with the output (12 biochemical responses) it was possible to identify which of the monitored variables were primary targets of the glycerol disturbance (namely: ATP, formate, acetyl-CoA synthase, isocitrate dehydrogenase, and isocitrate lyase), which were secondarily responsive (ethanol) and those that were independent (acetate, carnitine, lactate, and NADH/NAD ratio). Identification was achieved even though all the analyzed variables were affected by the pulse. (iv) Some variables exhibited uncorrelated dynamics despite their close functional relationship (ATP and NADH/NAD ratio, ethanol and lactate; carnitine and the crotonobetaine hydratase complex; acetate and the enzymes phosphotransacetylase, acetyl-CoA synthase and isocitrate lyase). The results are discussed in terms of E. coli transcriptional control, and it is concluded that glycerol pulse produces a stressing effect. The consequent activation of the polyamine-dependent mechanisms involved in such stressing effect provides a unified explanation for how glycerol uptake is down-regulated in the presence of high glycerol availability and how acetate can be produced without de novo biosynthesis.

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